title: Development of mass transport resistance in poly(lactide-co-glycolide) films and particles--a mechanistic study.
abstract: Poly(D,L-lactide-co-glycolide) (PLG) is the most frequently used biodegradable polymer in the controlled release of an encapsulated drug. The purpose of this work was to explain the surprisingly slow diffusion through this polymer, and locate the major source of mass transport resistance. Diffusion of human growth hormone (hGH) and glucose through PLG films was undetectable (using a diffusion cell), although the degraded polymer contained several times more water than polymer mass. In vitro release of hGH from PLG-coated particles also showed a surprisingly slow rate of release. Non-porous regions inside the PLG films were detected after three weeks of degradation using dextran-coupled fluorescent probes and confocal microscopy. The findings were supported by scanning electron microscopy. Diffusion through PLG films degraded for five weeks was significantly increased when the porosity of both surfaces was increased due to the presence of ZnCl(2) in the buffer the last 3 days of the degradation period. The results indicated high mass transport resistance inside the films after three weeks of degradation, and at the surfaces after five weeks of degradation. These results should also be applicable to microparticles of different sizes. Knowledge of the reason for transport resistance is important in the development of pharmaceuticals and when modifying the rate of drug release.
authors.affiliation: Department of Chemical Engineering, Lund University, P.O. Box 124, SE-221 00 Lund, Sweden. susanne.fredenberg@chemeng.lth.se
authors.forename: Susanne
authors.initials: S
authors.lastname: Fredenberg
authors.forename: Monica
authors.initials: M
authors.lastname: Jönsson
authors.forename: Timo
authors.initials: T
authors.lastname: Laakso
authors.forename: Marie
authors.initials: M
authors.lastname: Wahlgren
authors.forename: Mats
authors.initials: M
authors.lastname: Reslow
authors.forename: Anders
authors.initials: A
authors.lastname: Axelsson
mesh_terms: D002712:Chlorides / Q000737:chemistry; D003692:Delayed-Action Preparations; D004058:Diffusion; D004355:Drug Stability; D004356:Drug Storage; D005079:Excipients / Q000737:chemistry*; D005947:Glucose / Q000378:metabolism*; D019382:Human Growth Hormone / Q000378:metabolism*; D006801:Humans; D019344:Lactic Acid / Q000737:chemistry*; D008855:Microscopy, Electron, Scanning; D008863:Microspheres; D010316:Particle Size; D011100:Polyglycolic Acid / Q000737:chemistry*; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D014867:Water / Q000737:chemistry; D017967:Zinc Compounds / Q000737:chemistry
chemical_list: D002712:Chlorides; D003692:Delayed-Action Preparations; D005079:Excipients; D017967:Zinc Compounds; D014867:Water; D019382:Human Growth Hormone; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011100:Polyglycolic Acid; D019344:Lactic Acid; C016837:zinc chloride; D005947:Glucose